Regioselective cleavage of aromatic methyl ethers by methanesulphonic acid in the presence of methionine

摘要

2288 J.C.S. Perkin IRegioselective Cleavage of Aromatic Methyl Ethers by MethanesulphonicAcid in the Presence of MethionineBy Nobutaka Fujii, Hiroshi Irie, and Haruaki Yajima," Faculty of Pharmaceutical Sciences, Kyoto University,Kyoto, JapanAddition of methionine as a methyl group acceptor facilitates acidolysis of aromatic methyl ethers such as anisoleand p-methoxytoluene. Veratraldehyde and 4,5-dimethoxyindan-I -one gave isovanillin and 4-hydroxy-5-methoxyindan-I -one, respectively, indicating the usefulness of the reagent for regioselective cleavage.WE have noted previously the formation of S-methyl-methionine bismethanesulphonate salt along withphenol from methionine and methanesulphonic acid inthe presence of anisole. This suggested that themet hanesulphonic acid-met hionine system might beapplicable to the cleavage of aromatic ethers.Treatment of anisole with 1.1 equiv.of methionine and20 equiv. of methanesulphonic acid at room temperatureovernight gave phenol in 54 yield. G.1.c. of an n-hexane extract of the reaction mixture showed that thecleavage proceeded quantitatively . 9-Me t hox ytoluenegave $-cresol in 90 yield in the same manner. T.1.c.showed that both reactions were reasonably fast andclean. When 9-methoxyacetophenone was treated withthe same reagent at room temperature, no 9-hydroxy-acetophenone nor S-methylmethionine salts were detec-ted by t.1.c. Elevation of the reaction temperature (to60 "C) and prolongation of the reaction time (to 72 h)eventually gave 9-hydroxyacetophenone in 30 yield,accompanied by 367; of the starting material.Treatment of veratraldehyde with 1.1 equiv.ofmethionine and 20 equiv. of methanesulphonic acid at50 "C for 24 h furnished isovanillin in SSyO yield. Fur-thermore, 4,5-dimethoxyindan-l-one (1), treated simi-larly, gave 4-hydroxy-5-methoxyindan-l-one (2) in 70yield; the product showed a methoxy-singlet at 6 3.90in its n.m.r. spectrum solvent (CD,),SO. IrradiationOR0(1) R = Me( 2 ) R = Hat the frequency of the methyl signal caused an intra-molecular nuclear Overhauser effect (enhancement 22)on the signal of an aromatic proton responsible for acomponent of the AB-type quartet centred at 8 7.08,confirming that the remaining methoxy-group was atposition 5.These results indicate the usefulness of themethionine-methanesulphonic acid system for regio-selective cleavage of aromatic ethers.Although some sulphides other than methionine mayaccept alkyl groups in this reaction, methionine ispreferable because of its bifunctionality, which makesisolation of the phenolic product (s) convenient.Diethyl ether in the methionine-methanesulphonicacid system gave S-ethylmethionine ethyl ester, charac-terised as its dipicrate salt.EXPERIMENTALM.p.s were determined with a Yanagimoto microscope hot-stage apparatus. N.m.r. spectra were obtained with aVarian HA- 100 spectrometer (tetramethylsilane as internalstandard).Phenol from Anisole.-A mixture of anisole (540 mg,5 mmol), rnethionine (820 mg, 5.5 mniol), and methanesul-phonic acid (6.5 ml, ca.100 mmol) was kept a t room tempera-ture overnight, then thoroughly extracted with n-hexane.The extract was washed with a small amount of brine,dried, and evaporated to leave phenol (280 mg, 54).p-Cresol from p-Methoxyto1uene.-p-Methoxytoluene (243mg) was treated as above; the mixture was diluted withwater, and extracted with ether. The extract was washedwith brine, dried, and evaporated to leave p-cresol (198 mg,p-Hydroxyacetophenone from p-Methoxyacetophen0ne.-p-Methoxyacetophenone (158 mg) was treated with the samereagents a t 60 "C for 72 h to give p-hydroxyacetophenone(43 nig, 30) and starting material (36) by the usualwork- u p .Isovanillin from Veratra1dehyde.-Treatment of vera-traldehyde (330 nig) with niethionine (329 mg) and methane-sulphonic acid (2.6 nil) a t 50 "C for 24 h gave isovanillin(205 mg, 68).4-Hydroxy-5-methoxyindan- l-one (2) .--A mixture of 4,5-dimethoxyindan-l-one ( 1 ) (51 1 mg), methionine (436 mg),H. Irie, N.Fujii. H. Ogawa, H. Yajima, M. Fujino, and S.Shinagawa, .J.C.S. Chem. Comm., 1976, 022; Chem. and Pharm.Bull. ( . f a p a n ) . , in the press.90)1977 2289and methanesulphonic acid ( 3 . 5 ml) was set aside a t 22 'Cfor 72 h, then diluted with ice-water. The precipitate wascrystallised from acetone to give 4-hydroxy-5-methoxyindan-l-one (2) (332 mg, 70y0), m.p. 198-5202" (Found: C , 6 7 . 6 ;H , 5.6. C10H1003 requires C, 6 7 . 4 ; H, 5.7); vmax.(Nujol) 3 300-3 000 (OH) and 1 698 cm-l (CO); 6 (CD3)2-3.90 ( 3 H, s, OMe), 2.95 ( 2 H, t, J 5 Hz, H2-3), and 2.56 ( 2 H ,S-Ethylmethionine Ethyl Ester Dipicrate Salt.-A mixture ofSO 7 . 1 3 ( 1 H, d, J 8 Hz, H - 7 ) , 7 . 0 3 ( 1 H, d, J 8 Hz, H-6),t, J 5 Hz, H2-2).ether ( 1 . 1 ml), methionine (301 mg), and methanesulphonicacid ( 3 ml) was heated under reflux for 24 h and washedthoroughly with ether. The ether-insoluble residue wastaken up in a small amount of water. A saturated solutionof picric acid in water was added, to give S-ethylmethionineethyl ester dipicrate salt (540 mg), m.p. 67-74' (fromethanol) (Found: C, 3 8 . 3 ; H, 4.1; N, 14.6; S, 4.8. C,-H2,N02S,C,H2hT30,,C,H,N,0, requires C, 3 8 . 0 ; H, 3 . 8 ; K,1 4 . 8 ; S, 4.8).7/859 Received, 16th AZuy, 1977